title: Changes of placental syndecan-1 expression in preeclampsia and HELLP syndrome.
abstract: Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n = 8); (2) early-onset preeclampsia without (n = 7) and (3) with HELLP syndrome (n = 8); (4) preterm controls (n = 5); and (5) term controls (n = 9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n = 49) and controls (n = 32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p = 0.0001) and early-onset preeclampsia with or without HELLP syndrome (p = 0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.
authors.affiliation: Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Szabo
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Tibor
authors.initials: T
authors.lastname: Fule
authors.forename: Katalin
authors.initials: K
authors.lastname: Karaszi
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bhatti
authors.forename: Tibor
authors.initials: T
authors.lastname: Varkonyi
authors.forename: Ildiko
authors.initials: I
authors.lastname: Varkonyi
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenacs
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Papp
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovalszky
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005260:Female; D017359:HELLP Syndrome / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D053668:Syndecan-1 / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053668:Syndecan-1; D053778:Thiazolidines; C037068:latrunculin B